This Program Project is an integrated epidemiology and laboratory investigation of current critical issues in the epidemiology of lung cancer, the leading cause of cancer death in both men and women. It represents a collaborative effort by scientists in several disciplines, with the common theme of elucidating changes in lung cancer epidemiology, histology, and cigarette composition that may have major public health implications. In project 1 we propose a case-control study of lung cancer to pursue new leads with respect to observed differences in risk associated with both gender and race that may be related to differences in environmental/lifestyle factors (such as estrogen replacement) and metabolic factors (such as detoxification of carcinogens). Project 2 is a biomarker study with smokers of cigarettes with varying yields, whose goal it is to develop realistic estimates of actual biological dosage of nicotine and carcinogens from cigarette smoke. Project 3 will utilize metabolic and molecular techniques to investigate differences between Blacks and Whites in activation of certain tobacco-derived nitrosamines thought to be related to lung cancer, which is higher in Blacks, as well as detoxification of aromatic amines involved in bladder cancer, which is substantially lower in Blacks. Taken as a whole, this Program will significantly contribute to our knowledge of the cause and prevention of tobacco-related cancers, especially cancer of the lung.